In the field of transfusion, a whole-blood product, an erythrocyte product, a platelet product, a plasma product, and the like are used according to the need of recipients. In recent years, leukocyte-free blood transfusion in which a blood product is transfused after removing leukocytes contained in the blood product has been widely used. This is because it was found that relatively slight side effects accompanying blood transfusion, such as headache, nausea, chill, or febrile nonhemolytic reaction, or serious side effects which seriously affect a recipient, such as alloantigen sensitization, viral infection, or post-transfusion graft versus host disease (GVHD), are mainly caused by leukocytes contained in the blood product used for blood transfusion.
It is considered that relatively slight side effects such as headache, nausea, chill, and fever can be prevented by removing leukocytes in the blood product until the leukocyte residual rate becomes 10−1 to 10−2 or less. It is considered that leukocytes must be removed until the residual rate becomes 10−4 to 10−6 or less in order to prevent serious side effects such as alloantigen sensitization or viral infection.
In recent years, leukocyte-removing therapy using extracorporeal blood circulation has been conducted for treating diseases such as rheumatism or ulcerative colitis, and has achieved excellent clinical effects.
As a method for removing leukocytes from a blood product, a filter method of removing leukocytes using a filter material made from fiber mass such as nonwoven fabric or a porous structure with continuous pores has been most widely used due to advantages such as operational simplicity, low cost, and the like.
In the mechanism of leukocyte removal using the filter material such as fiber mass such as nonwoven fabric or a porous structure having continuous pores, it is considered that leukocytes coming into contact with the surface of the filter material adhere to or are adsorbed on the surface of the filter material. Therefore, as a means for improving the leukocyte-removing performance of the conventional filter material, a method of increasing the contact frequency between the filter material and leukocytes, specifically, studies of reducing the fiber diameter or the pore size of the nonwoven fabric or increasing the bulk density has been performed (see Patent Document 1). However, since the pressure drop is increased when causing the blood product to pass through the filter material accompanying improvement of the leukocyte-removing performance, there has been a problem that the filtration speed is significantly decreased before completing the filtration of a desired amount of blood.
On the other hand, as to the porous structure having continuous pores, a porous material having a bubble point of 0.08 to 0.3 kg/cm2 is disclosed as a leukocyte separation material free from clogging with leukocytes (see Patent Document 2). However, the inventors of the present invention have examined and found that this leukocyte separation material is suitable for reducing leukocytes contained in the blood product to 10−2 to 10−3, and possesses the following problem when using a porous material having a relatively small average pore diameter necessary for achieving a leukocyte residual rate of 10−4 which is the target value of the present invention. Specifically, although a filter exhibiting high leukocyte-removing performance can be obtained by using a porous material with an appropriate average pore diameter, such a porous material has a high pressure drop due to clogging of leukocytes and the like at the same time, resulting in a significant decrease of the blood filtration speed in the same manner as in the case of using nonwoven fabric having a small fiber diameter.
In recent years, the medical treatment field has posed additional demands for the leukocyte-removing filter. One of the demands is improvement of the recovery rate of useful components in addition to improvement of the leukocyte-removing performance. Blood as the raw material for the blood product is mainly valuable blood provided by a goodwill blood donation. However, uncollectible blood remaining in the leukocyte-removing filter is disposed of together with the filter and frittered away. Therefore, it is extremely meaningful to improve the recovery rate of useful components in comparison with the existing leukocyte-removing filter.
Therefore, in order to satisfy the above-described demand from the medical treatment field, a leukocyte-removing filter with a smaller amount of packed filter material by using a leukocyte-removing filter material having a high leukocyte-removing performance per unit volume has been demanded. Use of such a filter reduces the amount of blood remaining in the filter due to a reduction in the amount of filter material packed and makes it unnecessary to perform the operation of collecting useful components remaining in the filter, whereby the recovery rate of useful components is expected to be increased in comparison with a conventional filter.
As another demand for the leukocyte-removing filter in the market, there is a demand for treating a desired amount of blood in a short period of time. In order to satisfy such a demand, the leukocyte-removing filter is expected to have such a shape that the cross-sectional area of the filter is equal to or greater than that used in a conventional filter and the thickness of the filter material is reduced. It is necessary to increase the leukocyte-removing performance per unit volume in order to reduce the thickness of the filter material while maintaining the leukocyte-removing performance.
In order to satisfy such demands, attempts to improve the leukocyte-removing performance per unit volume have been made by increasing uniformity of property elements of the filter material. As a material in which the property elements of the filter material are made uniform in the technical field aiming at removing leukocytes, a leukocyte trapping material in which the volume of the pore section useful for leukocyte removal is increased by narrowing the pore size distribution (see Patent Document 3), and a three-dimensional mesh-like continuous porous material having a uniform pore size in which the ratio of the volume average pore diameter to the number average pore diameter is 1.5 to 2.5 (see Patent Document 4) have been proposed. As nonwoven fabric as the filter material, nonwoven fabric in which uniformity of the fiber diameter is improved by narrowing the fiber diameter distribution has been proposed (see Patent Documents 5 and 6).
In addition, it is known that the effective utilization factor of the filter material is improved by using nonwoven fabric with a formation index of 15 to 50 corresponding to a thickness of 0.3 mm as a filter material, because if such a filter material is used, blood flows evenly in the thickness direction of a filter in the entire filter area (see Patent Document 7).
In this manner, attempts to increase the leukocyte-removing performance per unit volume have been made by making the pore size or the fiber diameter and properties in the thickness direction of the filtration surface of the filter material uniform. However, the above prior arts are only concerned about the properties in the direction in which the liquid flows (i.e. the direction vertical to the filtration surface). Specifically, the prior art documents do not take into account the importance of a liquid flow while diffusing three-dimensionally and uniformly within a filter material. Even if uniformity of the pore size and fiber diameter is controlled in an optimal range, there is a limitation to the operation of avoiding or inhibiting clogging and increase of pressure drop, while improving leukocyte-removing performance per unit volume.
Therefore, a leukocyte-removing method satisfying the conflicting demands of excellent flowability and high leukocyte-removing performance in medical treatment field at the same time and a leukocyte-removing filter possessing sufficient performance have been desired.
[Patent Document 1] JP-B-H02-13587
[Patent Document 2] JP-A-H01-224324
[Patent Document 3] WO 93/03740
[Patent Document 4] JP-A-H07-124255
[Patent Document 5] JP-A-S63-175157
[Patent Document 6] JP-2811707
[Patent Document 7] WO 2004/050146